Swespine: the Swedish spine register : The 2012 report.

Swespine, the Swedish National Spine Register, has existed for 20 years and is in general use within the country since over 10 years regarding degenerative lumbar spine disorders. Today there are protocols for registering all disorders of the entire spinal column

The Swedish Spine Register: development, design and utility

The Swedish Spine Register enables monitoring of surgical activities focusing on changes in trends over time, techniques utilized and outcome, when implemented in general clinical practice. Basic requirements for a prosperous register are unity within the profession, mainly patient-based documentation and a well functioning support system. This presentation focuses on the development and design of the register protocol, problems encountered and solutions found underway. Various examples on how the results can be presented and utilized are given as well as validation. Register data demonstrate significant gender differences in lumbar disc herniation surgery with females having more pain, lower quality of life and more pronounced disability preoperatively while improvement after surgery is similar between genders. Quality of life after surgery for degenerative disorders is significantly improved for disc herniation, stenosis, spondylolisthesis and disc degenerative disorders. Over the last 10 years, surgical treatment for spinal stenosis has increased gradually while disc herniation surgery decreases regarding yearly number of procedures. An added function to the register enables more complex prospective clinical studies to include register data together with data suitable for the individual study. A common core set of demographic, surgical and outcome parameters would enable comparisons of clinical studies within and between nations

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.Peer reviewe

Plasma Cholesterol-Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (>= 80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-)Apob(100/100)Mttp(flox/flox)Mx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. Author Summary The main underlying cause of heart attacks and strokes is atherosclerosis. One strategy to prevent these often deadly clinical events is therefore either to slow atherosclerosis progression or better, induce regression of atherosclerotic plaques making them more stable. Plasma cholesterol lowering (PCL) is the most efficient way to induce atherosclerosis regression but sometimes fails to do so. In our study, we used a mouse model with elevated LDL cholesterol levels, similar to humans who develop early atherosclerosis, and a genetic switch to lower plasma cholesterol at any time during atherosclerosis progression. In this model, we examined atherosclerosis gene expression and regression in response to PCL at three different stages of atherosclerosis progression. PCL led to complete regression in mice with early lesions but was incomplete in mice with mature and advanced lesions, indicating that early prevention with PCL in individuals with increased risk for heart attack or stroke would be particularly useful. In addition, by inferring PCL-responsive gene networks in early, mature and advanced atherosclerotic lesions, we identified key drivers specific for regression of early (PPARG), mature (MLL5) and advanced (SRSF10/XRN2) atherosclerosis. These key drivers should be interesting therapeutic targets to enhance PCL-mediated regression of atherosclerosis

Measurement and prediction of outcome. Application in fusion surgery for chronic low backpain. The Swedish lumbar spine study

Background: Outcome of surgery for chronic low back pain should be documented ina standardised and reproducible fashion to establish evidence of its benefit. Measurementof outcome requires validated instruments, which have the ability to detect functionalchanges perceived as beneficial by the patient. The outcome instruments shouldbe practical in clinical decision-making and dependable in research conditions. Predictivefactors need to be isolated, and diagnostic instruments should be evaluated, toimprove the selection of surgical candidates.Aims: To validate a new instrument for measurement of physical function. To evaluatea simplification of over all outcome measurement. To establish the clinical importanceof outcome instrument score changes. To search for predictors of outcome. To evaluatethe predictive value of the pain-drawing.Study population: The main study population comprised 289 patients in the SwedishLumbar Spine Study, a multi-centre randomised controlled trial of surgery for chroniclow back pain. An age- and sex- matched control group of 287 randomly allocatedSwedish citizens, and four separate cohorts of patients treated surgically for variousspinal conditions were also employed.Procedures: The new instrument, The General Function Score, was tested for validityin a practical performance test, for reliability in a test-retest setting, and for responsivenessand feasibility, using the four separate cohorts. Simplification of outcome measurementwas tested by comparing retrospective patient global assessment with a set ofprospective multi-item outcome instruments, specifically evaluating responsiveness andbias. The minimal clinically important score changes of the General Function Score,the Oswestry Disability Index of physical disability, the Zung Depression Scale and theVisual Analogue Scale of pain, were estimated with patient global assessment as externalcriterion. The score changes were compared with the measurement errors of eachinstrument. Predictors of clinical outcome were evaluated by comparing base line characteristicsof patients with functional and occupational outcome. The pain-drawing wastested for predictive properties using four different interpretations of its features.Results and conclusions: The General Function Score demonstrated acceptable validity,reliability and feasibility. Patient global assessment appeared to be a valid outcomemeasure, which could replace multi-item outcome instruments in randomised controlledtrials of smaller sample size. The minimal clinically important score changes ofthe General Function Score, the Oswestry Disability Index and the Zung DepressionScale were less than the limits of the measurement errors and may, thus, not be detectedby the outcome instruments. The Visual Analogue Scale of pain was responsiveenough to confidently detect such a score change. Improved clinical outcome aftersurgical treatment was associated with non-neurotic personality traits and radiographicsigns of severe disc degeneration. Work resumption was associated with low age and ashort period of sick leave. No interpretation of the pain-drawing could predict theclinical outcome. A widespread pain-drawing was associated with a depressed state ofmood and high pain intensity, but not with personality traits

A health economic lifetime treatment pathway model for low back pain in Sweden

<p><b>Aims:</b> To develop a health economic model to evaluate the long-term costs and outcomes over the healthcare treatment pathway for patients with low back pain (LBP).</p> <p><b>Materials and methods:</b> A health economic model, consisting of a decision tree structure with a Markov microsimulation model at the end of each branch, was created. Patients were followed from first observed clinical presentation with LBP until the age of 100 years or death. The underlying data to populate the model were based on Swedish national and regional registry data on healthcare resource use and sickness insurance in patients presenting with LBP in the Swedish region Västra Götaland during 2008–2012. Costs (outpatient healthcare visits, inpatient bed days, pharmaceuticals, productivity loss), EUR 2016, and quality-of-life based on EQ-5D data from the registries and published estimates were summarized over the lifetime of the patients with 3% annual discount. A lost quality-adjusted life year (QALY) was valued at €70,000.</p> <p><b>Results:</b> Mean lifetime total cost was estimated at €47,452/patient, of which indirect costs were 57%. Total lifetime economic burden for all patients coming to clinical presentation in Sweden per year was €8.8bn. The average LBP patient was estimated to face a loss of 2.7 QALYs over their lifetime compared with the general population. For all patients in Sweden coming to clinical presentation in 1 year this gives 505,407 QALYs lost, valued at €35.3bn. Adding the economic burden, the total societal burden amounts to €44.1bn.</p> <p><b>Conclusion:</b> This pathway model shows that most patients with LBP receive conservative care, and a minority consume high-cost healthcare interventions like surgery. The model could be used to see broad economic effects of different patterns of healthcare provision in sub-groups with LBP and to estimate where it is possible to influence these pathways to increase utility for patients and for society.</p